DESCRIPTION

Hydroxocobalamin, the active ingredient in Cyanokit, is cobinamide dihydroxide
dihydrogen phosphate (ester), mono (inner salt), 3'-ester with 5,6-dimethyl-1-α-D-ribofuranosyl-1H-benzimidazole.
The drug substance is the hydroxylated active form of vitamin B12 and is a large
molecule in which a trivalent cobalt ion is coordinated in four positions by
a tetrapyrol (or corrin) ring. It is a hygroscopic, odorless, dark red, crystalline
powder that is freely soluble in water and ethanol, and practically insoluble
in acetone and diethyl ether. Hydroxocobalamin has a molecular weight of 1346.36
atomic mass units, an empirical formula of C62H89CoN13O15P
and the following structural formula:

The 5 g vial of hydroxocobalamin for injection is to be reconstituted with
200 mL of 0.9% NaCl, to give a dark red injectable solution (25 mg/mL). If 0.9%
NaCl is not readily available, 200 mL of either Lactated Ringers injection or
5% Dextrose injection (D5W) may be used as the diluent. Diluent is not included
in the Cyanokit. The pH of the reconstituted product ranges from 3.5 to 6.0.

INDICATIONS

Indication

Cyanokit is indicated for the treatment of known or suspected cyanide poisoning.

Identifying Patients with Cyanide Poisoning

Cyanide poisoning may result from inhalation, ingestion, or dermal exposure
to various cyanide-containing compounds, including smoke from closed-space fires.
Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic
plants, aliphatic nitriles, and prolonged exposure to sodium nitroprusside.

The presence and extent of cyanide poisoning are often initially unknown. There
is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions
must be made on the basis of clinical history and signs and symptoms of cyanide
intoxication. If clinical suspicion of cyanide poisoning is high, Cyanokit should
be administered without delay.

Table 1 : Common Signs and Symptoms of Cyanide Poisoning

Symptoms

Signs

Headache

Confusion

Dyspnea

Chest

tightness

Nausea

Altered Mental Status (e.g., confusion, disorientation)

Seizures or Coma

Mydriasis

Tachypnea / Hyperpnea (early)

Bradypnea / Apnea (late)

Hypertension (early) / Hypotension (late)

Cardiovascular collapse

Vomiting

Plasma lactate concentration ≥ 8 mmol/L

In some settings, panic symptoms including tachypnea and vomiting may mimic
early cyanide poisoning signs. The presence of altered mental status (e.g.,
confusion and disorientation) and/or mydriasis is suggestive of true cyanide
poisoning although these signs can occur with other toxic exposures as well.

Smoke Inhalation

Not all smoke inhalation victims will have cyanide poisoning and may present
with burns, trauma, and exposure to other toxic substances making a diagnosis
of cyanide poisoning particularly difficult. Prior to administration of Cyanokit,
smoke-inhalation victims should be assessed for the following:

Although hypotension is highly suggestive of cyanide poisoning, it is only
present in a small percentage of cyanide-poisoned smoke inhalation victims.
Also indicative of cyanide poisoning is a plasma lactate concentration ≥ 10
mmol/L (a value higher than that typically listed in the table of signs and
symptoms of isolated cyanide poisoning because carbon monoxide associated with
smoke inhalation also contributes to lactic acidemia). If cyanide poisoning
is suspected, treatment should not be delayed to obtain a plasma lactate concentration.

Use with Other Cyanide Antidotes

Caution should be exercised when administering other cyanide antidotes simultaneously
with Cyanokit, as the safety of co-administration has not been established.
If a decision is made to administer another cyanide antidote with Cyanokit,
these drugs should not be administered concurrently in the same intravenous
line. [See DOSAGE AND ADMINISTRATION.]

DOSAGE AND ADMINISTRATION

Comprehensive treatment of acute cyanide intoxication requires support of vital
functions. Cyanokit should be administered in conjunction with appropriate airway,
ventilatory and circulatory support.

Recommended Dosing

The starting dose of hydroxocobalamin for adults is 5 g administered as an
intravenous infusion over 15 minutes (approximately 15 mL/min). Administration
of the entire vial constitutes a complete starting dose. Depending upon the
severity of the poisoning and the clinical response, a second dose of 5 g may
be administered by intravenous infusion for a total dose of 10 g. The rate of
infusion for the second dose may r ange from 15 minutes (for patients in extremis)
to two hours, as clinically indicated.

Preparation of Solution for Infusion

The 5 g vial of hydroxocobalamin for injection is to be reconstituted with
200 mL of diluent (not provided with Cyanokit) using the supplied sterile transfer
spike. The recommended diluent is 0.9% Sodium Chloride injection (0.9% NaCl).
Lactated Ringers injection and 5% Dextrose injection (D5W) have also been found
to be compatible with hydroxocobalamin and may be used if 0.9% NaCl is not readily
available. The line on the vial label represents 200 mL volume of diluent. Following
the addition of diluent to the lyophilized powder, the vial should be repeatedly
inverted or rocked, not shaken, for at least 60 seconds prior to infusion.

Hydroxocobalamin solutions should be visually inspected for particulate matter
and color prior to administration. If the reconstituted solution is not dark
red or if particulate matter is seen after the solution has been appropriately
mixed, the solution should be discarded.

Incompatibility Information

Physical incompatibility (particle formation) and chemical incompatibility
were observed with the mixture of hydroxocobalamin in solution with selected
drugs that are frequently used in resuscitation efforts. Hydroxocobalamin is
also chemically incompatible with sodium thiosulfate and sodium nitrite and
has been reported to be incompatible with ascorbic acid. Therefore, these and
other drugs should not be administered simultaneously through the same intravenous
line as hydroxocobalamin.

Simultaneous administration of hydroxocobalamin and blood products (whole blood,
packed red cells, platelet concentrate and/or fresh frozen plasma) through the
same intravenous line is not recommended. However, blood products and hydroxocobalamin
can be administered simultaneously using separate intravenous lines (preferably
on contralateral extremities, if peripheral lines are being used).

Storage of Reconstituted Drug Product

Once reconstituted, hydroxocobalamin is stable for up to 6 hours at temperatures
not exceeding 40°C (104°F). Do not freeze. Any reconstituted product
not used by 6 hours should be discarded.

Storage

Cyanokit may be exposed during short periods to the temperature variations
of usual transport (15 days submitted to temperatures ranging from 5 to 40°C
(41 to 104°F), transport in the desert (4 days submitted to temperatures
ranging from 5 to 60°C (41 to 140°F)) and freezing/defrosting cycles
(15 days submitted to temperatures ranging from -20 to 40°C (-4 to 104°F)).

Reconstituted solution: Store up to 6 hours at a temperature not exceeding
40°C (104°F). Do not freeze. Discard any unused portion after 6 hours.

SIDE EFFECTS

Clinical Studies Experience

Because clinical trials were conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials may not reflect the rates observed
in practice.

Experience in Healthy Subjects

A double-blind, randomized, placebo-controlled, single-ascendingdose (2.5,
5, 7.5, and 10 g) study was conducted to assess the safety, tolerability, and
pharmacokinetics of hydroxocobalamin in 136 healthy adult subjects. Because
of the dark red color of hydroxocobalamin, the two most frequently occurring
adverse reactions were chromaturia (red-colored urine) which was reported in
all subjects receiving a 5 g dose or greater; and erythema (skin redness), which
occurred in most subjects receiving a 5 g dose or greater. Adverse reactions
reported in at least 5% of the 5 g dose group and corresponding rates in the
10 g and placebo groups are shown in Table 3.

Table 3 Incidence of Adverse Reactions Occurring in > 5%
of Subjects in 5 g Dose Group and Corresponding Incidence in 10 g Dose Group
and Placebo

ADR

5 g Dose Group

10 g Dose Group

Hydroxocobalamin
N=66
n (%)

Placebo
N=22
n (%)

Hydroxocobalamin
N=18
n (%)

Placebo
N=6
n (%)

Chromaturia (red colored urine)

66 (100)

0

18 (100)

0

Erythema

62 (94)

0

18 (100)

0

Rash*

13 (20)

0

8 (44)

0

Blood pressure increased

12 (18)

0

5 (28)

0

Nausea

4 (6)

1 (5)

2 (11)

0

Headache

4 (6)

1 (5)

6 (33)

0

Lymphocyte percent decreased

5 (8)

0

3 (17)

0

Infusion site reaction

4 (6)

0

7 (39)

0

* Rashes were predominantly acneiform

In this study, the following adverse reactions were reported to have occurred
in a dose-dependent fashion and with greater frequency than observed in placebo-treated
cohorts: increased blood pressure (particularly diastolic blood pressure), rash,
nausea, headache and infusion site reactions. All were mild to moderate in severity
and resolved spontaneously when the infusion was terminated or with standard
supportive therapies.

Other adverse reactions reported in this study and considered clinically relevant
were:

Experience in Known or Suspected Cyanide Poisoning Victims

Four open-label, uncontrolled, clinical studies (one of which was prospective
and three of which were retrospective) were conducted in known or suspected
cyanide-poisoning victims. A total of 245 patients received hydroxocobalamin
treatment in these studies. Systematic collection of adverse events was not
done in all of these studies and interpretation of causality is limited due
to the lack of a control group and due to circumstances of administration (e.g.,
use in fire victims). Adverse reactions reported in these studies listed by
system organ class included:

Adverse reactions common to both the studies in known or suspected cyanide
poisoning victims and the study in healthy volunteers are listed in the healthy
volunteer section only and are not duplicated in this list.

DRUG INTERACTIONS

No formal drug interaction studies have been conducted with Cyanokit.

Warnings & Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Emergency Patient Management

In addition to Cyanokit, treatment of cyanide poisoning must include immediate
attention to airway patency, adequacy of oxygenation and hydration, cardiovascular
support, and management of any seizure activity. Consideration should be given
to decontamination measures based on the route of exposure.

Allergic Reactions

Use caution in the management of patients with known anaphylactic reactions
to hydroxocobalamin or cyanocobalamin. Consideration should be given to use
of alternative therapies, if available.

Allergic reactions including angioneurotic edema have also been reported in
postmarketing experience.

Blood Pressure Increase

Many patients with cyanide poisoning will be hypotensive; however, elevations
in blood pressure have also been observed in known or suspected cyanide poisoning
victims.

Elevations in blood pressure ( ≥ 180 mmHg systolic or ≥ 110 mmHg diastolic)
were observed in approximately 18% of healthy subjects (not exposed to cyanide)
receiving hydroxocobalamin 5 g and 28% of subjects receiving 10 g. Increases
in blood pressure were noted shortly after the infusions were started; the maximal
increase in blood pressure was observed toward the end of the infusion. These
elevations were generally transient and returned to baseline levels within 4
hours of dosing.

Use of Blood Cyanide Assay

While determination of blood cyanide concentration is not required for management
of cyanide poisoning and should not delay treatment with Cyanokit, collecting
a pretreatment blood sample may be useful for documenting cyanide poisoning
as sampling post-Cyanokit use may be inaccurate.

Clinical Laboratory Evaluations

Because of its deep red color, hydroxocobalamin has been found to interfere
with colorimetric determination of certain laboratory parameters (e.g., clinical
chemistry, hematology, coagulation, and urine parameters). In-vitro tests indicated
that the extent and duration of the interference are dependent on numerous factors
such as the dose of hydroxocobalamin, analyte, methodology, analyzer, hydroxocobalamin
concentration, and partially on the time between sampling and measurement.

Based on in-vitro studies and pharmacokinetic data obtained in healthy volunteers,
the following table (Table 2) describes laboratory interference that may be
observed following a 5 g dose of hydroxocobalamin. Interference following a
10 g dose can be expected to last up to an additional 24 hours. The extent and
duration of interference in cyanide-poisoned patients may differ. Results may
vary substantially from one analyzer to another; therefore, caution should be
used when reporting and interpreting laboratory results.

Clinical Methods

Because of its deep red color, hydroxocobalamin may cause hemodialysis machines
to shut down due to an erroneous detection of a “blood leak”. This
should be considered before hemodialysis is initiated in patients treated with
hydroxocobalamin.

Photosensitivity

Hydroxocobalamin absorbs visible light in the UV spectrum. It therefore has
potential to cause photosensitivity. While it is not known if the skin redness
predisposes to photosensitivity, patients should be advised to avoid direct
sun while their skin remains discolored.

Patient Counseling Information

Cyanokit is indicated for cyanide poisoning and in this setting, patients will
likely be unresponsive or may have difficulty in comprehending counseling information.

Erythema and Chromaturia

Patients should be advised that skin redness may last up to 2 weeks and urine
coloration may last for up to 5 weeks after administration of Cyanokit. While
it is not known if the skin redness predisposes to photosensitivity, patients
should be advised to avoid direct sun while their skin remains discolored.

Rash

In some patients an acneiform rash may appear anywhere from 7 to 28 days following
hydroxocobalamin treatment. This rash will usually resolve without treatment
within a few weeks.

Pregnancy and Breast Feeding

Patients should be advised that maternal cyanide poisoning results in fetal
cyanide poisoning. Treatment for cyanide poisoning may be lifesaving for both
mother and fetus. Patients should notify their physician if they were pregnant
during therapy with Cyanokit [see Use In Specific Populations]. It is
not known whether hydroxocobalamin is excreted in human milk.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic
potential of hydroxocobalamin. Hydroxocobalamin was negative in the following
mutagenicity assays: in vitro bacterial reverse mutation assay using
Salmonella typhimurium and Escherichia coli strains, an in-vitro assay of the
tk locus in mouse lymphoma cells, and an in-vivo rat micronucleus assay.

The effect of hydroxocobalamin on fertility has not been evaluated.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies of Cyanokit in pregnant women.
In animal studies, hydroxocobalamin caused skeletal and visceral (soft tissue)
abnormalities at exposures (based on AUC) similar to human exposures at the therapeutic dose. Cyanokit should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus. Because cyanide readily crosses
the placenta, maternal cyanide poisoning results in fetal cyanide poisoning.
Timely treatment of the pregnant mother may be lifesaving for both mother and
fetus.

In animal studies, pregnant rats and rabbits received Cyanokit (75, 150, or
300 mg/kg/d) during the period of organogenesis. Following intraperitoneal dosing
in rats and intravenous dosing in rabbits, maternal exposures were equivalent
to 0.5, 1, or 2 times the human exposure at the therapeutic dose (based on AUC).
In the high dose groups for both species, maternal toxicity occurred, and there
was a reduced number of live fetuses due to embryofetal resorptions. In addition,
decreased live fetal weight occurred in high dose rats, but not in rabbits.
Incomplete skeletal ossification occurred in both rats and rabbits. In rats,
two fetuses of the high dose group and two fetuses of the mid dose group (each
from a different litter) had short, rudimentary or small front or hind legs.
Rabbit litters and fetuses exhibited a dose dependant increase in various gross
soft tissue and skeletal anomalies. The main findings in rabbits were flexed,
rigid flexor or medially rotated forelimbs or hindlimbs and domed heads at external
examination; enlarged anterior or posterior fontanelles of the ventricles of
the brain and flat, bowed or large ribs at skeletal examination; and dilated
ventricles of the brain, and thick wall of the stomach at visceral examination.

Labor and Delivery

The effect of Cyanokit on labor and delivery is unknown.

Nursing Mothers

It is not known whether hydroxocobalamin is excreted in human milk. Cyanokit
may be administered in life-threatening situations, and therefore, breast-feeding
is not a contraindication to its use. Because of the unknown potential for adverse
reactions in nursing infants, the patient should discontinue nursing after receiving
Cyanokit..

Pediatric Use

Safety and effectiveness of Cyanokit have not been established in this population.
In non-US marketing experience, a dose of 70 mg/kg has been used to treat pediatric
patients.

Geriatric Use

Approximately 50 known or suspected cyanide poisoning victims aged 65 or older
received hydroxocobalamin in clinical studies. In general, the safety and effectiveness
of hydroxocobalamin in these patients was similar to that of younger patients.
No adjustment of dose is required in elderly patients.

Renal Impairment

The safety and effectiveness of Cyanokit have not been studied in patients
with renal impairment. Hydroxocobalamin and cyanocobalamin are eliminated unchanged
by the kidneys. Oxalate crystals have been observed in the urine of both healthy
subjects given hydroxocobalamin and patients treated with hydroxocobalamin following
suspected cyanide poisoning.

Hepatic Impairment

The safety and effectiveness of Cyanokit have not been studied in patients
with hepatic impairment.

Overdosage & Contraindications

OVERDOSE

No data are available about overdose with Cyanokit in adults. Should overdose
occur, treatment should be directed to the management of symptoms. Hemodialysis
may be effective in such a circumstance, but is only indicated in the event
of significant hydroxocobalamin-related toxicity. Because of its deep red color,
hydroxocobalamin may interfere with the performance of hemodialysis machines
[see WARNINGS AND PRECAUTIONS].

CONTRAINDICATIONS

None

Clinical Pharmacology

CLINICAL PHARMACOLOGY

Mechanism of Action

Cyanide is an extremely toxic poison. In the absence of rapid and adequate
treatment, exposure to a high dose of cyanide can result in death within minutes
due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component
of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome
a3 prevents the cell from using oxygen and forces anaerobicmetabolism, resulting
in lactate production, cellular hypoxia and metabolic acidosis. In massive acute
cyanide poisoning, the mechanism of toxicity may involve other enzyme systems
as well. Signs and symptoms of acute systemic cyanide poisoning may develop
rapidly within minutes, depending on the route and extent of cyanide exposure.

The action of Cyanokit in the treatment of cyanide poisoning is based on its
ability to bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide
ion by substituting it for the hydroxo ligand linked to the trivalent cobalt
ion, to form cyanocobalamin, which is then excreted in the urine.

Pharmacodynamics

Administration of Cyanokit to cyanide-poisoned patients with the attendant
formation of cyanocobalamin resulted in increases in blood pressure and variable
changes in heart rate upon initiation of hydroxocobalamin infusions.

Pharmacokinetics

Following intravenous administration of hydroxocobalamin significant binding
to plasma proteins and low molecular weight physiological compounds occurs,
forming various cobalamin-(III) complexes by replacing the hydroxo ligand. The
low molecular weight cobalamins-(III) formed, including hydroxocobalamin, are
termed “free cobalamins-(III)”; the sum of free and protein-bound
cobalamins is termed “total cobalamins-(III)”. In order to reflect
the exposure to the sum of all derivatives, pharmacokinetics of cobalamins-(III)
(i.e. cobalamin-(III) entity without specific ligand) were investigated instead
of hydroxocobalamin alone, using the concentration unit μg eq/mL.

Dose-proportional pharmacokinetics were observed following single dose intravenous
administration of 2.5 to 10 g of hydroxocobalamin in healthy volunteers. Mean
free and total cobalamins-(III) Cmax values of 113 and 579 μg eq/mL, respectively,
were determined following a dose of 5 g of hydroxocobalamin. Similarly, mean
free and total cobalamins-(III) Cmax values of 197 and 995 μg eq/mL, respectively,
were determined following the dose of 10 g of hydroxocobalamin. The predominant
mean half-life of free and total cobalamins-(III) was found to be approximately
26 to 31 hours at both the 5 g and 10 g dose level.

The mean total amount of cobalamins-(III) excreted in urine during the collection
period of 72 hours was about 60% of a 5 g dose and about 50% of a 10 g dose
of hydroxocobalamin. Overall, the total urinary excretion was calculated to
be at least 60 to 70% of the administered dose. The majority of the urinary
excretion occurred during the first 24 hours, but red-colored urine was observed
for up to 35 days following the intravenous infusion.

When normalized for body weight, male and female subjects revealed no major
differences in pharmacokinetic parameters of free and total cobalamins-(III)
following the administration of 5 and 10 g of hydroxocobalamin.

Animal Pharmacology

Evidence of the effectiveness of hydroxocobalamin for treatment of cyanide
poisoning was obtained primarily from studies in animals due to the ethical
considerations of performing such controlled studies in humans. While the results
of these animal studies cannot be extrapolated to humans with certainty, the
extrapolation is supported by the understanding of the pathophysiologic mechanisms
of the toxicity of cyanide and the mechanisms of the protective effect of hydroxocobalamin
as examined in dogs. In addition, the results of uncontrolled human studies
and the animal study establish that hydroxocobalamin is likely to produce clinical
benefit in humans.

The effectiveness of hydroxocobalamin was examined in a randomized, placebo-controlled,
blinded study in cyanide-poisoned adult dogs assigned to treatment with vehicle
(0.9% saline), or 75 or 150 mg/kg hydroxocobalamin. Anesthetized dogs were poisoned
by intravenous administration of a lethal dose of potassium cyanide. Dogs then
received vehicle or 75 or 150 mg/kg hydroxocobalamin, administered intravenously
over 7.5 minutes. The 75 and 150 mg/kg doses are approximately equivalent to
5 and 10 g of hydroxocobalamin (respectively) in humans based on both body weight
and the Cmax of hydroxocobalamin (total cobalamins-(III)). Survival at 4 hours
and at 14 days was significantly greater in low-and high-dose groups compared
with dogs receiving vehicle alone (Table 4). Hydroxocobalamin reduced whole
blood cyanide concentrations by approximately 50% by the end of the infusion
compared with vehicle.

Clinical Studies

Smoke Inhalation Victims

A prospective, uncontrolled, open-label study was carried out in 69 subjects
who had been exposed to smoke inhalation from fires. Subjects had to be over
15 years of age, present with soot in the mouth and expectoration (to indicate
significant smoke exposure), and have altered neurological status. The median
hydroxocobalamin dose was 5 g with a range from 4 to 15 g.

Fifty of 69 subjects (73%) survived following treatment with hydroxocobalamin.
Nineteen subjects treated with hydroxocobalamin did not survive. Fifteen patients
treated with hydroxocobalamin were in cardiac arrest initially at the scene;
13 of these subjects died and 2 survived.

Two additional retrospective, uncontrolled studies were carried out in subjects
who had been exposed to cyanide from fire or smoke inhalation. Subjects were
treated with up to 15 g of hydroxocobalamin. Survival in these two studies was
34 of 61 (56%) for one study, and 30 of 72 (42%) for the second.

Cyanide Poisoning by Ingestion or Inhalation

A retrospective, uncontrolled study was carried out in 14 subjects who had
been exposed to cyanide from sources other than from fire or smoke (i.e., ingestion
or inhalation). Subjects were treated with 5 to 20 g of hydroxocobalamin. Eleven
of 12 subjects whose blood cyanide concentration was known had initial blood
cyanide levels considered to be above the lethal threshold.

Ten of 14 subjects (71%) survived, following administration of hydroxocobalamin.
One of the four subjects who died had presented in cardiac arrest. Of the 10
subjects who survived, only 1 subject had neurological sequelae at hospital
discharge. This subject had post-anoxicencephalopathy, with memory impairment,
considered to be due to cyanide poisoning.

Cross-Study Findings

Experience with Dosing Greater than 10 g of Hydroxocobalamin

Across all four uncontrolled studies, 10 patients who did not demonstrate a
full response to 5 or 10 g-doses of hydroxocobalamin were treated with more
than 10 g of hydroxocobalamin. One of these 10 patients survived with unspecified
neurological sequelae.

Effects on Blood Pressure

Initiation of hydroxocobalamin infusion as part of the therapeutic interventions
generally resulted in increases in blood pressure and variable changes in heart
rate (often normalization).

Survival of Patients Presenting in Cardiac Arrest

Of the 245 patients across all four studies, 68 (28%) presented in cardiac
arrest. While blood pressure and heart rate may have been restored in many of
these 68 patients, only five (7%) survived.

Skin and urine redness. Skin redness may last up to 2 weeks. Avoid
sun exposure while your skin is red. Urine redness may last up to 5 weeks.

Acne-like rash. An acne-like rash may appear 7 to 28 days after treatment
with Cyanokit. This rash usually goes away without any treatment.

Pregnancy. Be sure to tell your doctor immediately if you were pregnant
or think you may have been pregnant during treatment with Cyanokit. Treatment
for cyanide poisoning may save your life and the life of your unborn baby.

Breastfeeding. Talk to your doctor if you breastfeed your child.
The ingredient in Cyanokit may pass into your breast milk.

Talk to your doctor about any side effect that bothers you or that does not
go away.